An α1-adrenoceptor blocker (α1-blocker) is currently most often used as a drug for improving dysuria caused by benign prostatic hypertrophy, and as examples thereof, silodosin, tamsulosin hydrochloride, urapidil, naftopidil, terazosin hydrochloride hydrate, and the like can be given.
Currently, α1-blockers are mainly administered orally in clinical practice. However, in the case of oral administration, since a drug undergoes its metabolism (first-pass effect) in a digestive tract and liver, the number of administrations and the amount of dose may increase, and hence there are problems such as occurrence of side effects such as liver failure. In order to solve such problems, transdermal absorption preparations of the α1-blocker have been proposed. By making it into a transdermal absorption preparation, the drug efficacy is exerted sustainably for a long time, whereby the number of administrations and the amount of dose of the drug can be decreased, and advantages such as improvement of compliance due to a simplified administration, easiness of discontinuing the administration, or the like can be obtained.
Generally, a transdermal absorption preparation such as a skin patch is composed of a pressure-sensitive adhesive layer containing a drug, a backing for supporting the pressure-sensitive adhesive layer, and a release liner that covers the pressure-sensitive adhesive layer. The release liner is removed before using and applied to a prescribed place. In order to efficiently and sustainably exert the transdermal absorption action of the drug, it is necessary that the drug having a concentration as high as possible be dissolved in the pressure-sensitive adhesive (the drug solubility), and that said drug be sustainably released from the pressure-sensitive adhesive and be shifted to the skin (the release characteristics of a drug or the skin permeability of a drug). If the drug solubility is insufficient, crystals of the drug are formed in the pressure-sensitive adhesive, leading to a reduction in drug release, and hence a sufficient transdermal absorbability cannot be obtained. Furthermore, when it is impossible to achieve the intended amount of transdermal absorption by merely dissolving the drug in the pressure-sensitive adhesive, a prescribed transdermal absorption promoting agent must be added to increase the amount of transdermal absorption.
Several transdermal absorption preparations containing an α1-blocker have heretofore been proposed.
For example, Patent Document 1 discloses a percutaneous absorption preparation containing silodosin and a percutaneous absorption promoting agent such as oleyl alcohol, wherein the percutaneous absorption preparation further contains a fatty acid ester and/or a fatty acid amide that further improve the function of the percutaneous absorption promoting agent. In Patent Document 1, from the viewpoint that silodosin and the like have low skin permeability, and in order to use them in a skin-absorption type preparation wherein a drug is absorbed through the skin, their skin permeability must be increased, the above-mentioned fatty acid ester and/or fatty acid amide are used as essential components.
Furthermore, Patent Document 2 discloses a transdermal patch containing tamsulosin as an α1-blocker and an acrylic adhesive. Tamsulosin is slightly-soluble in various solvents and has a low solubility thereof relative to an adhesive, and hence there is a problem that when tamsulosin is used as it is, it exists in a crystalline state in the adhesive layer. For this reason, in Patent Document 2, a specific type of base resin having high performance of dissolving tamsulosin, that is, an acrylic adhesive based on a copolymer of a monomer having a pyrrolidone ring and a (meth)acrylic acid alkyl ester with a carbon atom number of the alkyl group of 4 to 12 is adopted as a base resin itself in the adhesive, and the solubility of tamsulosin in the adhesive layer is enhanced. In addition, it is described that tamsulosin can be dissolved in a higher concentration in the adhesive layer by using polyoxyethylene lauryl ether (lauromacrogol) preferably.